rs45506801

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004104.5(FASN):c.4188C>T(p.Tyr1396Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,611,624 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 13 hom., cov: 34)

Exomes 𝑓: 0.00092 ( 11 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.167

Publications

1 publications found

Variant links:

Genes affected

FASN (HGNC:3594): (fatty acid synthase) The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

FASN Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

FASN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-82085337-G-A is Benign according to our data. Variant chr17-82085337-G-A is described in ClinVar as Benign. ClinVar VariationId is 462052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.167 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00877 (1336/152312) while in subpopulation AFR AF = 0.0303 (1261/41574). AF 95% confidence interval is 0.0289. There are 13 homozygotes in GnomAd4. There are 649 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.4188C>T	p.Tyr1396Tyr	synonymous_variant	Exon 24 of 43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.4188C>T	p.Tyr1396Tyr	synonymous_variant	Exon 24 of 43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FASN	ENST00000306749.4 link	c.4188C>T	p.Tyr1396Tyr	synonymous_variant	Exon 24 of 43	1	NM_004104.5	ENSP00000304592.2	P49327
FASN	ENST00000634990.1 link	c.4182C>T	p.Tyr1394Tyr	synonymous_variant	Exon 24 of 43	5		ENSP00000488964.1	A0A0U1RQF0
FASN	ENST00000579410.1 link	n.245C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00871

AC:

1325

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00229

AC:

556

AN:

242364

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.00135

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000830

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

AF:

0.000924

AC:

1349

AN:

1459312

Hom.:

Cov.:

AF XY:

0.000851

AC XY:

618

AN XY:

725870

show subpopulations

African (AFR)

AF:

0.0332

AC:

1111

AN:

33456

American (AMR)

AF:

0.00166

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51818

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1111542

Other (OTH)

AF:

0.00179

AC:

108

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

182

274

365

456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00877

AC:

1336

AN:

152312

Hom.:

Cov.:

AF XY:

0.00871

AC XY:

649

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0303

AC:

1261

AN:

41574

American (AMR)

AF:

0.00372

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68008

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

128

191

255

319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00759

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FASN-related disorder

Benign:1

Sep 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epileptic encephalopathy

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.2

(source)

DANN

Benign

0.93

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over